epidemiology of infertility scotland

8/13/2019 Epidemiology of Infertility Scotland

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ORIGINAL ARTICLE Infertility

The epidemiology of infertility

in the North East of Scotland

S. Bhattacharya 1,4, M. Porter 1, E. Amalraj2, A. Templeton1,

M. Hamilton1, A.J. Lee2, and J.J. Kurinczuk 3

1Obstetrics and Gynaecology, University of Aberdeen, Aberdeen Maternity Hospital, Foresterhill, Aberdeen AB25 2ZD, UK 2The Centre of

Academic Primary Care, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK 3National Perinatal Epidemiology Unit, University of

Oxford Old Road Campus, Headington, Oxford OX3 7LF, UK

4Correspondence address: Tel: 01224 550590; Fax: 01224 559948; E-mail: [email protected]

background: There is a perception that the prevalence of infertility is on the rise. This study aimed to determine the current preva-

lence of infertility in a defined geographical population, ascertain changes in self-reported infertility over time and identify risk factors associ-

ated with infertility.

methods: A postal questionnaire survey of a random population-based sample of women aged 31–50 years was performed in the

Grampian region of Scotland. Questions addressed the following areas: pregnancy history, length of time taken to become pregnant each

time, whether medical advice had been sought and self-reported exposure to factors associated with infertility.

results: Among 4466 women who responded, 400 (9.0%) [95% CI 8.1, 9.8] had chosen not to have children. Of the remaining 4066

women, 3283 (80.7%) [95% CI 79.5, 82.0] reported no difficulties in having children and the remaining 783 (19.3%) [95% CI 18.1, 20.5] had

experienced infertility, defined as having difficulty in becoming pregnant for more than 12 months and/or seeking medical advice. In total 398

(9.8%) [95% CI 8.9, 10.7] women had primary infertility, 285 (7.0%) [95% CI 6.2, 7.8] had secondary infertility, 100 (2.5%) [95% CI 2.0, 2.9]

had primary as well as secondary infertility. A total of 342 (68.7%) and 208 (73.0%) women with primary and secondary infertility, respect-

ively, sought medical advice and 202 (59.1%) and 118 (56.7%) women in each group subsequently conceived. History of pelvic surgery, Chla-

mydial infection, endometriosis, chemotherapy, long-term health problems and obesity were associated with infertility. In comparison with a

similar survey of women aged 46–50 from the same geographical area, the prevalence of both primary infertility ( .24 months) [70/1081,

(6.5%) versus 68/710 (9.6%) P ¼ 0.02] and secondary infertility [29/1081 (2.7%) versus 40/710 (5.6%) P ¼ 0.002] were significantly lower.

conclusions: Nearly one in five women attempting conception sampled in this study experienced infertility, although over half of them

eventually conceived. Fertility problems were associated with endometriosis, Chlamydia trachomatis infection and pelvic surgery, as well as

obesity, chemotherapy and some long-term chronic medical conditions. There is no evidence of an increase in the prevalence of infertility

in this population over the past 20 years.

Key words: prevalence / risk factors / subfertility / epidemiology / infertility

Introduction

Infertility is defined as the inability to conceive following 12–24

months of exposure to pregnancy (Templeton et al . 1990). In 2002,

over 186 million women worldwide experienced problems conceiving.

This figure is higher than previous estimates, suggesting a global rise in

the prevalence of infertility (Farley, 1986, Rutstein and Shah, 2004). At

the turn of the last century projections of infertility in the United States

indicated a sharp upward trend over the next two decades (Stephen

and Chandra, 1998) while data from Europe suggested that increasing

numbers of couples were seeking assisted reproduction (Lutz and

Qiang, 2002). There is widespread concern about the effect of con-

tributory factors such as sexually transmitted infections like

Chlamydia trachomatis (Pal and Santoro, 2003; Karinen et al ., 2004),

deterioration in semen quality (Irvine et al ., 1996; Karinen et al .,

2004) and age-related decline in ovarian function in women

(Gosden and Rutherford, 1995; Dunson et al ., 2004) who choose

to postpone childbirth (Bhattacharya et al ., 2006; Goto et al ., 2006).

Results from existing studies suggest that the lifetime prevalence

of infertility is between 6.6% (Rostad et al ., 2006) and 32.6%

(Marchbanks et al ., 1989). This wide variation could reflect actual

population-based differences, but is more likely to be due to differ-

ences in defining and measuring infertility (Rachootin and Olsen,

1982; Page, 1989; Greenhall and Vessey,1990; Templeton et al .,

1991; Gunnell and Ewings, 1994; Schmidt and Munster, 1995;

Philippov et al ., 1998; Wyshak, 2001; Gnoth et al ., 2003; King,

& The Author 2009. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.

For Permissions, please email: [email protected]

Human Reproduction, Vol.24, No.12 pp. 3096–3107, 2009

Advanced Access publication on August 14, 2009 doi:10.1093/humrep/dep287



2003; Rostad et al ., 2006). Few recent studies have been based on

self-reported data from a representative population. Fewer still have

covered the full spectrum of reproductive experience including miscar-

riages and ectopic pregnancies (Maconochie et al ., 2004) or addressed

secular trends (Stephen and Chandra, 1998) in the prevalence of infer-

tility. A recent reproductive survey in the UK (Oakley et al ., 2008) has

reported that 2.4% women aged 40–55 had never been pregnant

(despite having tried) and 16% of them had consulted a doctor

about this. Despite a large sample size of 6580 women, this study

was not designed to provide data on how long women had tried for

a pregnancy or to examine the association between lifestyle and

medical factors and infertility.

A population-based study on the prevalence of infertility was con-

ducted in Grampian in 1988 (Templeton et al ., 1991). The stable

population in the north-east of Scotland, coupled with access to the

tools used in this previous postal survey offered the unique opportu-

nity of performing a study on the epidemiology of infertility in the same

geographical area at the present time. In the present study we aimed

to establish the current prevalence of infertility, ascertain changes in

self-reported infertility over time and to identify risk factors associated

with infertility.

MethodsA cross-sectional study was undertaken. Data were collected by means of

a population-based postal survey of women aged 31–50 years living in

Grampian, Scotland in 2007. Women were identified from the Community

Health Index (CHI) which lists everyone who is registered with a general

practitioner in Scotland. As all individuals in the UK are expected to reg-

ister with a general practitioner, CHI effectively covers all women living in

Scotland who access any form of primary, secondary or tertiary health

care or screening (such as cervical screening).The CHI number for an indi-

vidual contains date of birth, a number to represent sex and a personal

identifier. A randomly selected sample of 9000 women was sent an invita-

tion to participate from the office of the Director of Public Health (DPH)

along with an information sheet, a self-completion questionnaire and reply-

paid envelope. Responses were logged and reminder letters and a second

complete mailing were sent to non-responders (by the DPH Office) to

maximize the response. Questionnaires were completed anonymously

and the identities of the respondents were not known to the researchers.

The questionnaire was structured and largely pre-coded for ease of data

entry, and incorporated identical questions from the previous study

(Templeton et al ., 1991) conducted in this area in 1988 as well as some

new questions on lifestyle factors. Questions addressed the following

domains:

Reproductive history : Current and past use of contraception, pregnancy

history including miscarriages, terminations and ectopic pregnancies,

births, time to each pregnancy and whether medical advice was sought

for fertility problems.

Medical and lifestyle information: General health, medical history perti-

nent to fertility problems, current levels of smoking, drinking and exercise,

current height and current weight, and an assessment of quality of life using

the Euroquol scale (Brochs and EuroQOL Group., 1996).

Demographic information: Age, marital status, educational level, own

occupation and partner’s occupation. Deprivation was assessed by

linkage of the responder postcodes to The Scottish Index of Multiple

Deprivation (SIMD, 2006) which is a small area statistic of deprivation

derived from 37 indicators across the seven domains of: income, employ-

ment, health, education skills and training, geographic access to services,

housing and crime. The first quintile corresponds to the least deprived

and the fifth quintile the most deprived zones. Age and SIMD 2006 quintile

data were available from the CHI for the non-responders.

We assumed a 60% response after two mailings to 9000 women which

would generate 5400 completed questionnaires. Taking the prevalence of

primary and secondary infertility to each be in the range of 6– 8%

(Templeton et al ., 1990) 5400 responses would enable us to estimate

the current prevalence of infertility with a 95% confidence interval of

+1%. Under these assumptions this sample size would yield 700

women with infertility (either primary or secondary infertility or both)who would form the basis of a nested, unmatched, case–control analysis

to explore factors associated with infertility. With the estimated 700 cases

this analysis would have 80% power to detect, at the 5% level of statistical

significance, an odds ratio of 1.5 or greater for exposures with a

prevalence in the controls ranging from 15 to 70% and an odds ratio of

2.0 or greater for exposures ranging from 5 to 90%.

The data from the completed questionnaires were entered into a study-

specific database by trained data entry staff, and checked, cleaned and ana-

lysed using SPSS (Statistical Package for the Social Sciences; IL, USA).

To enable comparison with published data we defined infertility in three

different ways: unsuccessful attempted conception for 12 months or

longer (in line with current clinical practice); unsuccessful attempted con-

ception for 24 months or longer (for comparison with data from the 1988

survey); (Templeton et al ., 1990) and unsuccessful attempted conceptionfor 12 months or longer and/or had sought medical help with conception

(Schmidt et al ., 1995). The latter definition was derived to ensure the

inclusion of women with a prior history of successful fertility treatment

who had sought a second course of treatment without attempting spon-

taneous conception for 12 months or longer and older women who, in

line with current clinical practice, may be referred early for treatment,

that is before attempting conception for 12 months. Primary infertility

refers to problems with conceiving a first pregnancy and secondary infer-

tility to conception problems in any subsequent pregnancy. Data are

reported for the whole cohort (31–50 years) and for age groups 36–

40 years and 46–50 years to correspond with the results reported by

Templeton et al . (1990).

Ninety-five per cent confidence intervals (95% CIs) of prevalence esti-

mates were derived. Basic descriptors were compared across infertilitygroups by univariate analyses using the chi-square test, independent

t -test and Mann–Whitney U -test as appropriate. Unconditional logistic

regression modelling was used to explore the independent relationship

between demographic, medical and lifestyle factors, and infertility status.

Variables considered as potential confounders were those which had

shown a univariate association at P , 0.10. A forward stepwise procedure

was employed and a final parsimonious model was derived by the removal

of factors which did not significantly contribute to the fit of the model using

a P -value of less than or equal to 0.05. The study was approved by the

North of Scotland Research Ethics Service.

ResultsA total of 4522 women completed and returned the questionnaire, a

response of 50.2% (Table I). Responders were similar in mean (SD)

age to overall study sample [40.9 (5.6) years versus 41.0 (5.5)

years, respectively] but were less likely to live in a socially deprived

area: [12.6 versus 17.2% in SIMD 2006 categories 4 and 5,

respectively].

The mean (SD) number of children among responders was 1.75

(1.31). Of the 4522 women who responded to the questionnaire,

56 had not yet tested their fertility, and were excluded from further

analysis. These women were significantly younger than those included

Epidemiology of infertility 3097



in the analysis (P , 0.001); 52% were 35, 23% were 36–40, 11%

were 41–45 and 14% were 46–50 years of age. For women whose

fertility had been tested, the corresponding percentages were 21,27, 27 and 26% respectively.

Among 4466 women, 400 women (9%) specifically reported avoid-

ing pregnancy and were voluntarily childless, and this was the case for

5.8% (n ¼ 67) of women aged 46–50 years. Based on duration alone,

82.5% (n ¼ 3356) of the cohort of 4066 women reported no difficulty

in becoming pregnant using the 12 month cut-off, and 90.9% ( n ¼

3681) reported no difficulty when the 24 month cut-off was applied

(Table II).

Among those women who attempted conception (n ¼ 4066)

the prevalence of primary infertility alone was 10.5% based on the

12 month time to conception cut-off and 5.9% based on the

24 month cut-off. Secondary infertility alone affected 5.3% of

women using the 12 month cut-off and 2.9% using the 24 monthfigure. A small number of women experienced both primary and

secondary infertility: 1.7 and 0.3% according to the 12 month and

24 month cut-offs, respectively. Overall, 17.5% of women experi-

enced difficulty conceiving at some stage in their life when the

12 month cut-off was applied and 9.1% reported the same experience

when the 24 month definition was used. There was no evidence of a

significant trend in the prevalence of infertility across the different

age groups of women when the definition was based on duration of

infertility alone. The prevalence of primary unresolved infertility

(women with no pregnancies at all despite trying) was 4.0% in the

entire cohort and 4.1% in women aged 46–50 years.

Using the definition of infertility based on both duration and/or

having sought medical help with conception, the overall prevalence

estimates of infertility increased for both the time to conception

cut-offs to 19.3% for the 12 month time to conception cut-off and

11.8% for the 24 month cut-off (Table III). Using the time to con-

ception cut-off of 12 and 24 months, respectively in combination

with seeking medical help resulted in prevalence estimates of: 9.8

and 5.7% for primary infertility alone; 7.0 and 5.2% for secondary

infertility alone; and 2.5 and 0.9% for both primary and secondary

infertility. There was no increase in the prevalence of infertility with

increasing age groups when the definition was based on a duration

of either 12 months or .24 months as well as health seeking

behaviour. Overall 4.1% of women who attempted conception

never conceived a first pregnancy and this was the case for 4.2% of

women aged 46–50 years.

Of all those with infertility, 145 (73.6%) women aged between 36

and 40 years and 145 (67.1%) between 46 and 50 years had sought

medical advice about their inability to conceive (P ¼ 0.15). This

included a total of 342 (68.7%) and 208 (73.0%) women with

primary and secondary infertility, respectively. Slightly, although not

significantly, more women aged 36–40 years with primary infertility

had sought medical help in comparison with women aged 46–50

years (71.0 versus 64.5%, respectively; P ¼ 0.25). The corresponding

proportions for secondary infertility were 78.8 and 71.8% ( P ¼ 0.33).

Among those who sought help, 202 (59.1%) women with primary

infertility and 118 (56.7%) with secondary infertility ultimately con-

ceived. However, we were unable to confirm from the questions

we asked on this subject (which were the same asked in the previous

study) if these pregnancies occurred with or without active treatment.

In comparison, spontaneous pregnancies occurred in 88 (56.4%)

women with primary and 72 (93.5%) with secondary infertility.

Overall, 58.2% (290/498) of women with primary infertility eventually

conceived, as did 66.7% (190/285) of those with secondary infertility(Table III). The outcomes of all the pregnancies of the infertile and

fertile groups are given in Table IV. Women who experienced inferti-

lity were significantly more likely to have had a spontaneous pregnancy

loss, an ectopic pregnancy and a stillbirth but less likely to have had a

legal termination of pregnancy. Whilst the proportion of live births was

similar for the primary infertility and fertile groups the proportion was

significantly lower in the secondary infertility group.

The commonest self-reported causes of infertility were ovulation

problems, sperm quality problems and unexplained infertility

(Table V). Some women reported more than one cause of their infer-

tility: 129 (77.2%) women reported one, 29 (16.4%) reported two,

and nine women (5.1%) reported three causal factors contributing

to their primary infertility; and 124 (82.1%) women reported one,21 (13.9%) reported two, and six (4.0%) reported three factors in

relation to their secondary infertility.

The relationship between demographic, medical and lifestyle factors

and ever having experienced infertility (primary, secondary or both)

were explored (Table VI). Women who had experienced infertility

were more likely (P , 0.05) to be obese and to report a lower

quality of life score on the Euroquol scale; other lifestyle and demo-

graphic indicators were not significantly different between the

groups. In contrast, as regards medical and reproductive indicators,

the infertile group was significantly more likely to report a history of

tubal surgery, other pelvic surgery, appendicectomy and/or endome-

triosis; a history of Chlamydial infection; a history of chemotherapy

and long-term health problems. They were significantly less likely to

report intrauterine contraceptive device (IUCD), use of surgical ster-

ilization (either of themselves or their partners).

Educational status, previous pelvic surgery or endometriosis, che-

motherapy, Chlamydial infection, long-term health problems, pack

years of cigarette smoking and BMI were included in the logistic

regression model. We did not include male and female sterilization vari-

ables in the model because these interventions are more commonly

offered to couples who have completed their family than they are a

cause of infertility. For a similar reason we did not include IUCD use

in the model. Although potentially associated with infertility, an IUCD

........................................................................................

Table I Response to postal questionnaires

Outcome First

mailing

April–May

2007, N

Second

mailing

June –July

2007, N

Total, N

(%)

Questionnaire

completed

3316 1206 4522 (50.2)

Refused to

participate

950 256 1206 (13.4)

Questionnaire sent

to wrong address

and ineligible

subjects

92 29 121 (1.4)

Did not respond 4642 3151 3151 (35.0)

Total mailed 9000 4642 9000 (100.0)

3098 Bhattacharya et al.



............................................................................................................... ......................................................

.................................................................................................................................................................................................

Table II Prevalence of infertility and eventual conception based on duration of attempting conception only

Duration of at least 12 months Duration of at least 24 months

Entire cohort, age 31–

50 years, n 5 4466a,f

,N (%)

Age 31–

35 years,n5 922,

N (%)

Age 36–

40 years,n 5 1189,

N (%)

Age 41–

45 years,n 5 1206,

N (%)

Age 46–

50 years,n 5 1149,

N (%)

Entire cohort, age 31–

50 years, n 5 4449b,f

N (%)

Age 31–

35 years,n5 917,

N (%)

Primary

infertility

426 (10.5) [9.5–11.4]d 93 (12.2) 110 (10.0) 108 (9.6) 115 (10.6) 239 (5.9) [5.2–6.6]d 49 (6.5)

Never

conceived

162 (4.0) 37 (4.9) 37 (3.4) 44 (3.9) 44 (4.1) 136 (3.4) 27 (3.6)

Eventually

conceived

264 (6.5) 56 (7.4) 73 (6.7) 64 (5.7) 71 (6.6) 103 (2.5) 22 (2.9)

Primary and

secondary

infertility

67 (1.7) [1.3–2.0]d 11 (1.5) 20 (1.8) 14 (1.2) 22 (2.0) 13 (0.3) [0.2 –0.5]d 1 (0.1)

Not pregnant 8 (0.2) 2 (0.3) 5 (0.5) 1 (0.1) 0 (0.0) 2 (0.05) 0 (0.0)

Becamepregnant

59 (1.6) 9 (1.2) 15 (1.4) 13 (1.2) 22 (2.0) 11 (0.3) 1 (0.1)

Secondary

infertility

217 (5.3) [4.7–6.0]d 45 (5.9) 50 (4.6) 67 (6.0) 55 (5.1) 116 (2.9) [2.4 – 3.4]d 22 (2.9)

Not pregnant 27 (0.7) 14 (1.8) 8 (0.7) 1 (0.1) 4 (0.4) 25 (0.6) 12 (1.6)

Became

pregnant

190 (4.7) 31 (4.1) 42 (3.8) 66 (5.9) 51 (4.7) 91 (2.3) 10 (1.3)

Total

infertility c710 (17.5) [16.3–18.6]d 149 (19.6) 180 (16.4) 189 (16.8) 192 (17.7) 368 (9.1) [8.2–10.0]d 72 (9.5)

No infertility 3356 (82.5) [81.4– 83.7]d 612 (80.4) 917 (83.6) 937 (83.2) 890 (82.3) 3681 (90.9) [90.0–91.8]d 684 (90.5)

Overall

Totale4066 761 1097 1126 1082 4049 756

Voluntary

childlessness

400 (9.0) [8.1–9.8]d 161 (17.5) 92 (7.7) 80 (6.6) 67 (5.8) 400 (9.0) [8.2–9.8]d 161 (17.6)

aExcludes 56 and b73 women with untested fertility.cTotal of primary, secondary and primary as well as secondary.d95% Confidence intervals for prevalence.eOverall Total includes Total infertility as well as No infertility.f Includes Total infertility, No infertility as well as Voluntary childlessness.

b y g u e s t o n F e b r u a r y 9 , 2 0 1 1 h u m r e p . o x f o r d j o u r n a l s . o r g D o w n l o a d e d f r o m

http://humrep.oxfordjournals.org/





























is also a common form of contraception for women who have

completed their child bearing. The mutually adjusted results are given

in Table VII. Pelvic conditions, chemotherapy, Chlamydial infection,

long-term health problems and obesity were each independently

associated with an increase in the odds of infertility.

Comparison with previous Grampian data Table VIII shows that in comparison with the previous study

(Templeton et al ., 1990) on the same geographical population, the

current proportion of women aged 46–50 with a history of infertility

of 24 months or longer duration was significantly lower [99/1081,

(9.2%) versus 108/710 (15.2%) than in the past (P , 0.001).

Discussion

Our results suggest that nearly one in five women of reproductive age

attempting conception experience infertility; one in 25 women at the

end of their reproductive years never conceived a desired pregnancy;

and 1 in 11 is childless by choice. There is no evidence of an increase

in the proportion of women with infertility over the past two decades.Factors independently associated with infertility include current

obesity, a history of long-term health problems, chemotherapy,

pelvic problems (endometriosis and surgery) and Chlamydial infection.

This study follows on from an earlier one (Templeton et al ., 1990)

in the same geographical area and used identical questions pertaining

to trying for and time to achieve each pregnancy in a large random

sample of women. In addition, we are able to comment on the associ-

ation of common lifestyle factors and medical conditions with inferti-

lity. As measuring prevalence of infertility is always contentious

(Gnoth et al ., 2005), we have used a number of alternative definitions

for this condition. Obtaining current demographic and lifestyle data

avoided any bias due to self-reporting of historical information,

although we acknowledge the limitations of using these data as aproxy for historical information.

One of the potential shortcomings of this project is the response

rate of just over 50%. This is lower than our previous study

(Templeton et al ., 1990, 1991) and others conducted more than a

decade ago (Buckett and Bentick, 1997) but higher than a recent

reproductive survey in the UK (Oakley et al ., 2008) which had a

response rate of 46%. We attempted to minimize non-response by

sending two mailings of the questionnaires, but unlike some of the pre-

vious studies (Templeton et al ., 1990; Buckett and Bentick, 1997)

which had a response rate of 85.7 and 85%, respectively, were

unable to contact non-responders by telephone which would have

compromised anonymity. In accordance with previous reports

(Schmidt and Munster, 1995) and in common with postal surveys in

general we found differences in socio-economic position between

responders and non-responders, although they did not differ in their

age distributions. This socio-economic disparity may have led to a

slight under estimate of the true prevalence of infertility. The profile

of our populations of responders was similar to that of participants

in the Scottish Health Survey (The Scottish Government) for

women of the same age. Responders who smoked reported similar

levels of mean daily cigarette intake (13.7 versus 14.9 in the Health

Survey), those who drank reported a similar mean weekly alcohol

intake (7.0 versus 6.5 units) and overall 36.9% of responders versus

.............................................................................................................................................................................................

Table IV Outcomes of all pregnancies in fertile and infertile* women

Women with primary

infertility † (n 5 498)

N (%)

Women with secondary

infertility (n5 285)

N (%)

Women with no

infertility (n 5 3283)

N (%)

P -value (across all

three groups)

Births 598 (79.8) 555 (74.1) 6778 (78.9) ,0.001

Stillbirth 9 (1.2) 12 (1.6) 52 (0.6)

Spontaneous miscarriages 110 (14.7) 167 (22.3) 1013 (11.8)

Ectopic pregnancies 11 (1.5) 6 (0.8) 66 (0.8)

Terminations 19 (2.5) 7 (0.9) 673 (7.8)

Molar pregnancies 2 (0.3) 2 (0.3) 10 (0.1)

Total pregnancies 749 (100) 749 (100) 8592 (100)

Molar pregnancies were combined with terminations for applying chi-square test.

*Unsuccessful attempted conception for 12 months or longer and/or had sought medical help with conception.†Includes women with both primary and secondary infertility.

........................................................................................

Table V Self-reported cause of infertility amongst

women who reported a diagnosis*

Diagnosis** Primary

infertile group

(n 5 167)

N (%)

Secondary

infertile group

(n5 151)

N (%)

P -value

Ovulation

problems

54 (32.3) 35 (23.2) 0.069

Sperm quality

problems

49 (29.3) 36 (23.8) 0.268

Blocked

fallopian tubes

20 (12) 21 (13.9) 0.607

Unexplained

infertility

49 (29.3) 45 (29.8) 0.928

Endometriosis 19 (10.7) 15 (10) 0.677

Others 23 (13.8) 32 (21.2) 0.081

*Unsuccessful attempted conception for 12 months or longer and/or had sought

medical help with conception.

**Women have reported more than one diagnosis.




.............................................................................................................................................................................................

Table VI Demographic, lifestyle and medical factors in women with and without experience of infertility*

Factor Category Experienced infertility*

(n 5 783)

N (%)

No infertility*

(n5 3283)

N (%)

P -value

Demographic factors

†Age 41.11 (5.6) 41.19 (5.4) 0.703

Currently employed Yes 613 (78.5) 2654 (81.0) 0.129

Social deprivation (SIMDEC,

2006 quintiles)

1-Least deprived 271 (34.6) 1158 (35.3) 0.491

2 239 (30.5) 992 (30.2)

3 166 (21.1) 738 (22.5)

4 73 (9.3) 292 (8.9)

5-Most deprived 34 (4.3) 103 (3.1)

Partner in employment Yes 676 (88.8) 2790 (87) 0.39

Education None 68 (8.7) 242 (7.4) 0.078

High School 295 (37.9) 1369 (42.1)

College-University 416 (53.4) 1643 (50.5)

Marital status Single 38 (4.9) 135 (4.1) 0.313

Separated/Divorced/Widow 78 (10.0) 389 (11.9)

Living with partner 83 (10.6) 376 (11.5)

Married 583 (74.6) 2376 (72.5)

Own occupation Managerial/Professional 152 (25.2) 587 (22.4) 0.318

Intermediate 241 (39.9) 1068 (40.7)

Routine & Manual occupation 211 (34.9) 969 (36.9)

Partners’ occupation Managerial/Professional 230 (35.1) 1061 (39.0%) 0.115

Intermediate 133 (20.3) 480 (17.6)

Routine & Manual Occupation 293 (44.7) 1183 (43.4)

Medical factors

IUCD use Yes 159 (20.4) 814 (24.9) 0.009

Tubal sterilization Yes 71 (9.2) 481 (14.9) 0.001

Partner sterilized Yes 172 (26.4) 1001 (34.8) 0.001

Past history of any of the

following:

Yes 231 (29.5) 610 (18.6) 0.001

Tubal surgery

Pelvic surgery

Appendicectomy

Endometriosis

Chemotherapy Yes 12 (1.5) 21 (0.6) 0.023

Past Chlamydial infection Yes 45 (5.7) 116 (3.5) 0.006

Long-term health problems** Yes 160 (20.5) 493 (15.1) 0.001

Lifestyle factors

Body mass index ,20 (underweight) 36 (4.6) 198 (6.3) 0.003

20–24.99 (normal weight) 334 (44.1) 1513 (48.2)

25–29.00 (over weight) 220 (29.0) 896 (28.5)

30 (obese) 168 (22.2) 533 (17.0)

Smoking status Current or ex-smoker 318 (41.5) 1315 (41.2) 0.916

Never smoked 449 (58.5) 1879 (58.8)

†Cig/day 15 (10–20) 12 (10– 20) 0.166

Alcohol use Within the last 7 days 537 (68.8) 2288 (69.8) 0.616

†Units consumed per week 5 (3– 10) 6 (3–9) 0.873

Strenuous exercise Exercise .1 h/week 262 (33.5) 1037 (31.6) 0.449

Exercise 0.25 to 1 h/week 186 (23.8) 762 (23.2)

No Exercise 335 (42.8) 1484 (45.2)

Moderate exercise .2 h/week 30 (3.8) 145 (4.4) 0.697

1–2 h/week 268 (34.2) 1075 (32.7)

0.25 to 1 h/week 313 (40.0) 1364 (41.5)

None 172 (22.0) 699 (21.3)

Continued




33.0% in the Health Survey reported taking 30 min of moderate exer-

cise per week. Furthermore the average family size of 1.75 reported

by responders is consistent with current national figures for Scotland

(General Register Office for Scotland, 2007). National surveys such

as the Scottish Health Survey are unlikely to attract a 100% response

or be completely free of bias. Thus, although the profile of responders

in our study is similar to that of those in the Scottish Health Survey we

acknowledge that this does not guarantee the fact that we have

obtained responses from a representative sample of the population.

Our current estimate of 4.1% for the prevalence of primary unre-

solved infertility in women aged 46–50 was very similar to results

from the same area 20 years ago (Templeton et al ., 1990) and com-

parable to the 2.7– 4.5% prevalence rate quoted in a review of the

.............................................................................................................................................................................................

TableVI Continued

Factor Category Experienced infertility*

(n5 783)

N (%)

No infertility*

(n 5 3283)

N (%)

P -value

Mild exercise .2 h/week 35 (4.5) 147 (4.5) 0.981

1– 2 h/week 321 (41.0) 1332 (40.6)

0.25 to 1 h/week 277 (35.4) 1187 (36.2)None 150 (19.2) 617 (18.8)

Engagement in leisure activity

to sweat

Never/rarely 224 (29.2) 963 (30.1) 0.823

Sometimes 374 (48.7) 1520 (47.5)

Often 170 (22.1) 718 (22.4)

†Quality of life score

(Euroquol)

77.66 (16.9) 79.55 (16.0) 0.005

†Pack years of cigarette

smoking (excluding never

smokers)

10 (5.0–17.3) 10 (4.13–16.0) 0.083

*Unsuccessful attempted conception for 12 months or longer and/or had sought medical help with conception. Percentages based on responses.

**Self-reported long-term health problems include asthma (48), hypothyroidism (14), diabetes (6), arthritis (12), depression (1) and other (17).

†Values are mean (SD) or median (IQR).

........................................................................................

Table VII Health and lifestyle factors associated with

infertility*

Adjusted odds ratio1 (95% CI)

Pelvic problems** 1.8 (1.5 –2.2)

Chemotherapy 2.1 (1.02 –4.5)

Chlamydial infec tion 1.6 (1.1 – 2.3)

Long-term health problemsþþ 1.3 (1.1–1.6)

BMI

20–24.99—normal weight 1.0

,20—under weight 0.9 (0.6 – 1.3)

25 – 29—overweight 1.1 (0.9 – 1.4)

30—obese 1.4 (1.1–1.7)

*Unsuccessful attempted conception for 12 months or longer and/or had sought

medical help.

þOdds ratios mutually adjusted for all the variables reported in the table.

**Tubal surgery, other pelvic surgery, appendicectomy or endometriosis.

11Self-reported long-term health problems include asthma (48), hypothyroidism

(14), diabetes (6), arthritis (12), depression (1) and other (17).

........................................................................................

Table VIII Comparison of infertility prevalence

between the 1988 (Templeton et al ., 1990) and 2007

(present study)

Category 1988 survey, age

46–50 years,

infertility >24

months

(n 5 766)**

N (%)

2007 study, age

46–50 years,

infertility >24

months,

(n 5 1148)**

N (%)

P -value

Primary infertility only 56 (7.9) 67 (6.2) 0.166

Never pregnant 27 (3.8) 42 (3.9)

Ever pregnant 29 (4.1) 25 (2.3)

Primary &

Secondary

infertility

12 (1.7) 3 (0.3) 0.001

Not pregnant 8 (1.1) 0

Became

pregnant

4 (0.6) 3 (0.3)

Secondary

infertility only

40 (5.6) 29 (2.7) 0.001

Not pregnant 17 (2.4) 4 (0.4)

Becamepregnant

23 (3.2) 25 (2.3)

Total

Infertility

108 (15.2) 99 (9.2) ,0.001

No infertility 602 (84.8) 982 (90.8)

Overall Total* 710 1081

Voluntary

Childlessness

56 (7.3) 67 (5.8) 0.197

*Overall Total includes total infertility and No infertility & percentages are based on

overall total.

**Includes total infertility, no infertility and voluntary childlessness.




literature in 1995 (Schmidt and Munster, 1995). Two recent UK

surveys in 1997 and 2008 both reported a figure of 2.4% (Buckett

and Bentick, 1997; Oakley et al ., 2008).

Some estimates of causes of infertility have been clinic based

(Collins et al ., 1983; Hull et al ., 1985; Katyama et al ., 1989;

Maheshwari et al ., 2008) In contrast, population-based figures are

available (Rachootin and Olsen, 1982; Greenhall and Vessey, 1990;

Thonneau et al ., 1991; Schmidt et al ., 1995; Buckett and Bentick,

1997). Direct comparisons are difficult due to alternative ways of

defining categories and presenting male and female factors

separately (Thonneau et al ., 1992). It is difficult to interpret data on

self-reported causes of infertility as not all couples who experience

problems are fully investigated and responses may be subject to

recall bias. However, despite these limitations, except for a higher

prevalence of male factor infertility, our results are consistent with

those of Buckett and Bentick (1997) one of the more recently

conducted UK population-based studies.

Our results suggest that the overall conception rate in women with

fertility problems was 56.1% which corresponds to previously reported

figures of 38–48% (Collins et al ., 1983; Hull et al ., 1985; Katyama et al .,

1989; Templeton et al ., 1991; Collins et al ., 1994). Of those who con-ceived, 83.8 and 78.9% in women with primary and secondary infertility,

respectively, went on to give birth as compared with 78% in both

groups in the study by Templeton et al . (1991).

Our results confirm previously reported associations between infer-

tility and pelvic-related factors, including pelvic surgery (including

appendicectomy), tubal surgery and sexually transmitted infection

(Thonneau et al ., 1992). We found no significant association

between infertility and current levels of exercise. With the exception

of regular strenuous exercise, which has been linked to hypothalamic

anovulation and amenorrhoea, this has been the finding of other

similar studies (Homan et al ., 2007). We were able to confirm a sig-

nificant association between infertility and current obesity (BMI

30) but not between infertility and other factors reported byHoman et al . (2007) such as current or past smoking, or current

alcohol use. Interpretation of these findings, especially those relating

to smoking, needs to take into account the fact that observed associ-

ations may not be causal, especially given the difficulty of trying to

relate current lifestyle data to events that occurred in the past.

There is ongoing debate about the definition of infertility (Greenhall

and Vessey., 1990; Gnoth et al ., 2005) as well as the appropriate

numerator and denominator used to determine prevalence. Numer-

ators have included lifetime childlessness, lifetime failure to conceive,

lack of conception over a defined period of time (12 or 24 months)

and seeking medical help (Schmidt and Munster, 1995; Oakley et al .,

2008). Denominators have included the whole population of

women of reproductive age, eligible members of the whole population

(i.e. those who have had a chance to attempt conception), age

cohorts, peri-menopausal women and post-menopausal women.

Inclusion of the whole population or even the entire eligible population

is likely to underestimate prevalence, as does a focus on younger

cohorts of women who have not yet reached the end of their child-

bearing years. Restricting the sample to a post-menopausal population

can result in a biased sample as women with major medical problems

who have a lower survival rate may not be included. This would also

be unhelpful if one is interested in the current size of the infertility

problem from a service provision point of view.

In this study we not only considered women who had tried for a

pregnancy for over 12 months, but also women with a shorter/

unknown duration who had sought medical help for infertility. Since

the latter more closely reflects current clinical practice, we used this

expanded definition for much of the analysis. In terms of primary infer-

tility, either definition yielded similar prevalence rates—indicating that

very few women sought medical help before 12 months. A significant

minority of women (n ¼ 68) with unresolved secondary infertility of

unknown duration sought medical advice without success before

they eventually stopped trying for a baby. We chose to include

them in our infertile group on pragmatic grounds, given that they

had not conceived despite the passage of time. This highlights the

problem with the traditional time-driven definitions of infertility in con-

temporary practice which is characterized by higher public awareness

of infertility (Porter and Bhattacharya, 2008) and early access to

medical services (Oakley et al ., 2008).

In terms of the denominator, we have used the cohort of eligible

women of reproductive age (31–50 years) whose fertility had been

tested. Although we have excluded women with voluntary childless-

ness and those yet to test their fertility, given the current trend

towards delaying the first pregnancy (Maheshwari et al ., 2008) wemay have underestimated the full extent of infertility in younger

women. Menopausal women offer the best opportunity to collect

data on lifetime prevalence of infertility, but inclusion of younger

women allows a better estimate of current reproductive patterns as

well as health seeking behaviour. In this study we have attempted to

do both.

Most studies assessing the prevalence of infertility have been cross

sectional. Despite some early clinic-based work, it is generally believed

that they should be population based, as in this study. Along with most

other studies on infertility, we have used self-reported information.

This has been shown to be reliable and valid for fertility-related data

(Joffe, 1989; Baird et al ., 1991; Zielhuis et al ., 1992). We have

chosen to enquire about actively trying for a pregnancy as well aslack of regular contraception use, reflecting women’s actual behaviour

when contemplating conception (Greil and McQuillan, 2004).

Interpretation of the results of this study needs to take into account

the methods used to define the condition. Our results on lifetime infe-

cundity (absence of any pregnancies) which are least susceptible to

reporting or recall bias are consistent with previous reports.

Although subject to a greater degree of uncertainty, our data on

prevalence do not support an increase in infertility, regardless of the

age cohort or the criteria used to define it. The substantial difference

between the prevalence of primary and secondary infertility suggests

that, as many women seek medical advice and treatment well before

24 months, fewer women than in the past are likely to wait as long as

this, and any definition based on this interval is likely to underestimate

the prevalence of infertility. It seems likely that more women are

seeking medical help early. This is possibly due to greater awareness

of fertility issues among women (Porter et al ., 2006) and the effect of

published guidelines (The Royal College of Obstetricians and Gynaecol-

ogists; National Collaborating Centre for Women’s and Children’s

Health, 2004) suggesting early intervention in cases where there is a

known fertility problem or where the woman is older.

In previous studies, the number of women seeking medical help has

been variously reported as: 25%; (Hirsch and Mosher, 1987) 47.1%;

(Schmidt et al ., 1995) 23–32%; (Rachootin and Olsen, 1981) 44.8%




(Gunnell and Ewings, 1994). In this study, two-thirds of women with

primary and three-quarters with secondary infertility sought medical

help. With 73.6% of women aged 36–40 and 67.1% of women

aged 46–50 in the present study seeking medical help for infertility,

it appears that Templeton et al ., 1991 earlier figures of 76.5% (36–

40 years) and 62.0% (46–50 years) might have been an overestimate

or could reflect societal changes over time.

Compared with previous data from the same geographical area

(Templeton et al ., 1990), the proportion of women (aged 46–50 years)

with infertility of 24 months duration is lower, although the overall preva-

lence of infertility based on a 12 month definition is similar. This apparent

fall in the numberof women withinfertility of 24 months probably reflects

social andmedical changes in thelast twodecades which have encouraged

a more proactive approach to fertility investigations and treatment. Thisis

consistent with current guidelines on infertility in the UK (The Royal

College of Obstetricians and Gynaecologists; National Collaborating

Centre for Women’s and Children’s Health, 2004) which suggest early

investigationsand treatment in older women andin those with known fer-

tility problems, sometimes even earlier than 12 months. These factors

make it difficult to be confident about an actual fall in the prevalence of

infertility. What is less in doubt, is the fact that there is no evidence tosuggest an increase in the prevalence of infertility. This is broadly consist-

ent with recent data from the USA (Stephen and Chandra, 2006) which

suggest a decrease in infertility rates between 1982 and 2002 as well as

other reports from Europe which do not suggest an increase in time to

pregnancy (Joffe, 2000; Jensen et al ., 2005; Scheike et al ., 2008).

Knowledge about the extent of clinically defined infertility in a popu-

lation is essential to health professionals, health policy-makers and

government in terms of planning healthcare services. Within the UK

there is now formal recognition that infertility is a clinical problem

and there is a commitment by the NHS to fund evidence-based treat-

ment. Critical to the implementation of recommendations made by

the National Institute of Health and Clinical Excellence (NICE;

National Collaborating Centre for Women’s and Children’s Health,2004) in Expert Advisory Group in Infertility Services in Scotland

(EAGISS) is an accurate assessment of the prevalence of infertility in

order to cost and plan service delivery. Awareness about risk

factors associated with infertility is also important in terms of health

promotion. Our results confirm existing data in the literature on the

association between obesity, pelvic problems, including Chlamydial

infection and infertility, which can be translated in terms of useful

and potentially effective public health messages.

The results of this study do not support the view that the preva-

lence of infertility has increased, but do suggest that women are

seeking medical help earlier. This work needs to be replicated on a

larger scale in a wider population to confirm the broader applicability

of the results to the general UK population. Our findings also expose

the weaknesses of current definitions of infertility and emphasize the

need for more methodological work in this area.

Conclusions

The overall prevalence of infertility in a randomly sampled population

of women attempting conception between 31 and 50 is 19.3%.

Nearly 4% of women have unresolved infertility at the end of their

reproductive lives and 9% report being voluntarily childless. Infertility

is associated with endometriosis, Chlamydia trachomatis infection and

pelvic surgery as well as obesity, chemotherapy and some long-term

chronic medical conditions. There is no evidence of an increase in

the prevalence of infertility in this population over the past 20 years.

Contributions

S.B. was the Principal Investigator. He designed the study, led the

funding application, wrote the protocol, managed the project, inter-preted the data and results and wrote the first draft of the paper.

M.P. helped to design the study and to write the funding application.

She designed and piloted the questionnaire, managed the initial

phase of the project, supervised data entry and contributed to the

interpretation of results. A.L. helped design and supervised the statisti-

cal analysis, interpreted the data and results and helped to draft the

paper. E.A.R. performed the statistical analysis and helped interpret

the results. A.T. co-conceived the project, designed the original ques-

tionnaire on which the present version is based, and contributed to

study design and interpretation of results. M.H. helped in the initiation

of the project, study design and interpretation of results. J. K.

co-conceived the study and co-wrote the funding application. She

advised on the study and questionnaire design, data analysis, interpret-

ation of data and had a major input into the final draft of the paper. All

authors commented on and contributed to the final version of this

paper.

Acknowledgements

We would like to thank all the women who completed the question-

naire. Professor Pat Doyle, London School of Hygiene & Tropical

Medicine, commented on study design. Ms Debbie Willox provided

secretarial support and formatted the document.

Funding

The Chief Scientist Office, Scotland funded the study. The views

expressed are those of the authors and not the funding body.

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Submitted on December 5, 2008; resubmitted on May 5, 2009; accepted on July 14, 2009


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